GENE MUTATED IN CANCER FOUND
IN SOME WITH AUTISM

COLUMBUS, Ohio – A gene that is changed in many forms of cancer
has also been found to show similar changes in some forms of autism, according
to preliminary research.

The gene, known as PTEN,
was found to be changed, or mutated, in three of 18 people with larger
than normal heads and autism spectrum disorder. Autism
spectrum disorder includes classical autism, Rett
syndrome and other conditions.

Inherited gene mutations in the PTEN gene are seen in Cowden
syndrome, a poorly recognized disorder that increases a person’s
risk of developing cancers of the breast, thyroid and uterus. PTEN mutations
are also found in several non-inherited (i.e., spontaneous) cancers, including
thyroid and endometrial cancers and some brain tumors.

The findings, published in the April Journal
of Medical Genetics, raise the possibility that some people with
autism and large heads may have an increased risk of cancer.

“If our findings are verified, I think that patients with classical
autism or autism spectrum disorders and who have large heads should be
offered genetic counseling and testing for PTEN mutations,” says
principal investigator Charis
Eng, professor of internal
medicine and director of the clinical
cancer genetics program at the OSU CCC-James.

“If our findings
are verified, I think that patients with classical autism or autism
spectrum disorders and who have large heads should be offered genetic
counseling and testing for PTEN mutations.”

“Those with PTEN mutations should be offered cancer surveillance
like anyone with Cowden syndrome or other syndromes involving PTEN mutations
and an elevated risk of cancer.”

PTEN is a tumor-suppressor gene, and normally helps prevent cells from
becoming cancerous. When a mutation silences tumor-suppressor genes, it
can place a person at higher-than-usual risk of developing cancer during
his or her lifetime.

Autism is a developmental disorder that typically appears by age 3.
It has a prevalence of four to 10 cases per 10,000 people. It is three
to four times more common in males than females. People with autism typically
show impaired social interactions; impaired verbal and nonverbal communications;
repeated body movements, such as hand flapping or rocking; attachment
to objects; and resistance to changes in routine.

This study involved 18 children 3 to 18 years of age and diagnosed with
ASD and having an enlarged head, a condition known as macrocephaly. The
patients’ head circumference placed them in the 97th to 99th percentile
for head size for their age and sex.

Twelve of the 18 patients were identified during clinic visits; six,
who had classic autism and macrocephaly, were selected from the Autism
Genetic Resource Exchange, a gene bank for autism.

Of the 18 patients, three males (17 percent) age 2 to 4 years showed
mutations in the PTEN gene. The locations of the mutations in the PTEN
gene are different from those seen in people with cancer, Eng notes, but
that may not matter.

“Tumor suppressor genes can be silenced in many ways,” she
says, “and if the gene does not function, it can raise the lifetime
risk of cancer.”

The paper’s first author is Merlin G. Butler, Children’s
Mercy Hospitals and Clinics. Other OSU researchers involved in this study
were Xiao-Ping Zhou, research scientist, and Robert Pilarski, genetic
counselor.

Funding from the Children’s Mercy Hospitals Special Gift Funds,
the Children’s Mercy Hospitals Physician Scientist Award, the Hall
Foundation and the American
Cancer Society supported this research.